In this study, a series of 3-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole derivatives were designed, synthesized, and evaluated for their biological activities. Upon performing kinase assays, most of the compounds exhibited potent inhibition against JAK2/3 and Aurora A/B with the IC₅₀ values ranging from 0.008 to 2.52 μM. Among these derivatives, compound 10e expressed the most moderate inhibiting activities against all the four kinases with the IC₅₀ values of 0.166 μM (JAK2), 0.057 μM (JAK3), 0.939 μM (Aurora A), and 0.583 μM (Aurora B), respectively. Moreover, most of the derived compounds exhibited potent cytotoxicity against human chronic myeloid leukemia cells K562 and human colon cancer cells HCT116, while compound 10e expressed antiproliferative activities against K562 (IC₅₀₌6.726 μM). According to western blot analysis, compound 10e down-regulated the phosphorylation of STAT3, STAT5, Aurora A, and Aurora B in a dose-dependent manner in K562 and HCT116 cells. Cell cycle analysis revealed that compound 10e inhibited the proliferation of cells by inducing cell cycle arrest in the G2 phase. The molecular modeling suggested that compound 10e could maintain a binding mode similar to the binding mode of AT9832, a common JAK 2/3 and Aurora A/B kinases multi-target kinase inhibitor. Therefore, compound 10e might be a potential agent for cancer therapy deserving further research.

在这项研究中，一系列的3-（4-苯基-1H-咪唑-2-基）-1H-吡唑衍生物被设计，合成并评估了它们的生物学活性。在进行激酶测定后，大多数化合物表现出对JAK2 / 3和Aurora A / B的有效抑制作用，IC ₅₀值为0.008至2.52μM。在这些衍生物中，化合物10e对所有四种激酶表现出最适度的抑制活性，IC ₅₀值为0.166μM（JAK2），0.057μM（JAK3），0.939μM（Aurora A）和0.583μM（Aurora B），分别。此外，大多数衍生化合物对人慢性髓细胞性白血病细胞K562和人结肠癌细胞HCT116均显示出强大的细胞毒性，而化合物10e表达了针对K562的抗增殖活性（IC _{50 =} 6.726μM）。根据蛋白质印迹分析，化合物10e在K562和HCT116细胞中以剂量依赖性方式下调STAT3，STAT5，Aurora A和Aurora B的磷酸化。细胞周期分析表明，化合物10e通过诱导G2期细胞周期停滞来抑制细胞增殖。分子模型表明化合物10e可以维持与AT9832的结合模式相似的结合模式，AT9832是常见的JAK 2/3和Aurora A / B激酶多​​靶点激酶抑制剂。因此，化合物10e可能是潜在的癌症治疗药物，值得进一步研究。